Thursday, May 24, 2007
Cheah et al.[Nature] show that expression of the NMT1 gene is regulated at the level of pre-mRNA alternative splicing by a riboswitch that binds to thiamine pyrophosphate (TPP). a, At low concentrations of TPP, the TPP-binding (aptamer) region of the riboswitch base-pairs with sequences surrounding a splice site (red blocking line) in a nearby non-coding sequence, and prevents its selection by the splicing machinery. A distal splice site (green arrow) is selected, however, resulting in the generation of a shorter NMT1 mRNA with a coding sequence, or open reading frame (ORF), that translates into a functional NMT1-encoded protein (green signal). b, At high TPP levels, the aptamer undergoes a conformational rearrangement so that the region that was previously bound to the nearby splice site is now used to bind to TPP. This and other conformational changes (not shown) generate a longer mRNA splice variant that contains short, 'decoy' ORFs (red signal), preventing functional NMT1 expression.